Method for monitoring intraocular pressure using a passive intraocular pressure sensor and patient worn monitoring recorder

ABSTRACT

A device for passively measuring intraocular pressure of a patient including an in vivo sensor and an instrument external to the patient for remotely energizing the sensor, thereby permitting the instrument to determine the intraocular pressure. The device directly and continuously measures the intraocular pressure of a patient. The in vivo sensor in the intraocular pressure monitor includes a capacitive pressure sensor and an inductive component. An instrument, external to the patient, measures the pressure, provides readout of the pressure values and determines the intraocular pressure.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. provisional application No.60/162,793, filed on Nov. 1, 1999.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates to a method and device for monitoring intraocularpressure. Intraocular pressure, the pressure of fluid within an eye,takes on significance with respect to glaucoma and its treatment.

The glaucomas are a group of diseases that constitute a public healthproblem of staggering proportions. An estimated 5-10 million Americanshave an intraocular pressure (IOP) greater than 21 mm Hg on routineoffice testing, placing them at increased risk of suffering glaucomatousoptic nerve damage. Conservatively estimated, approximately 2 millionAmericans have glaucoma, while only 1 million patients are undergoingtreatment. Nine hundred thousand Americans have some degree of visionimpairment, and 80,000 patients are legally blind as a result ofglaucoma.

Many factors are known to influence IOP, which accounts for the widefluctuations noted in both the normal and glaucomatous population.Diurnal variation in IOP may frequently reach 6 mm Hg, and dailypressure peaks may reach 30 mm or more. Pressure spikes resulting fromeye squeezing or rubbing can reach much higher levels. These pressurepeaks may not be detected clinically, thus resulting in misdiagnosed, orundiagnosed glaucoma. Some glaucoma patients carry the diagnosis ofnormal tension glaucoma. While this group of diseases may represent anabnormal sensitivity of the optic nerve to seemingly normal IOP, it mayalso represent an inadequate sampling of IOP, which misses periods ofsignificant IOP elevation. Thus, at least a subgroup of glaucomapatients may not be diagnosed, or treated, until a significantprogression in their disease has been detected. The optimal frequencyfor measuring IOP has yet to be determined. Routine office visits areoften spaced 3-4 months apart. Visits are more frequent during periodsof medication adjustment. Following eye surgery, IOP measurements may berequired every few hours. More than 3 million office visits each yearare devoted to monitoring IOP in patients who are either being treatedfor glaucoma, or who are suspected of having glaucoma. Substantialhealthcare resources are devoted to the task of monitoring IOP, and eventhis effort may represent a sub-optimal surveillance strategy.

2. Description of the Related Art

As a physiological parameter, IOP is important in its correlation withocular fluid mechanics, muscular action, hemodynamics, and glaucomadiseases. For over three decades, medical, biomedical, and engineeringprofessionals have been developing methods, devices and instruments toobtain accurate measurements of dynamic intraocular pressure.Conventional ophthalmotonometers (COT) are useful to this end, but, ingeneral, they do not offer the features desired for certain ocularresearch and therapy. The medical needs are to continuously and“conveniently” monitor internal-to-the eye hydrostatic pressure inambulatory subjects—these attributes are lacking in COT.

One of the earliest attempts to obtain accurate measurements ofintraocular pressure by direct contact with the internal fluids of theeye is described by Collins, Miniature Passive Transensor for Implantingin the Eye, IEEE TRANSACTIONS ON BIO-MEDICAL ENGINEERING, Vol. BME-14,No 2, April 1967.

Work in this area during the following two decades indicates thecontinued need for and interest in obtaining dynamic, real-timeintraocular pressure measurements. Few of the advances in this area takea direct measurement of the eye's internal pressure, that is, by havingthe hydrostatic pressure of eye fluids acting directly on a sensor. Inmost cases, IOP was inferred using various active and passive pressuresensors in contact with the external globe, sclerotic or cornea, of theeye. Examples of active pressure sensors include strain gauge typesensors. Examples of passive pressure sensors include self-resonant typesensors.

More recent efforts are described in Schnell et al., “Measurement ofIntraocular Pressure by Telemetry in Conscious Unrestrained Rabbits,”INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol. 37, No. 6, pp.958-965, May 1996, and McLaren et al., “Continuous Measurement ofIntraocular Pressure in Rabbits by Telemetry, ” INVESTIGATIVEOPHTHALMOLOGY & VISUAL SCIENCE, Vol. 37, No. 6, pp. 966-975, May 1996.Schnell and McLaren utilized technology commercially available from DataSciences International of St. Paul, Minn., to obtain hydrostatic IOPwithin the midvitreous and aqueous humor, respectively.

SUMMARY OF THE INVENTION

The present invention provides a method and apparatus for directly andcontinuously monitoring intraocular pressure.

The present invention concerns a device for measuring intraocularpressure (IOP) of a patient (an IOP monitoring system). The IOPmonitoring system includes an in vivo sensor. The sensor includes acapacitive pressure sensor and an inductive component. An excorporal(external to the patient) instrument remotely measures the pressure inthe eye, provides readout of pressure values and energizes the sensor,thereby permitting the instrument to determine the intraocular pressure.

Additionally, the present invention relates to a method for measuringintraocular pressure of a patient. A signal is generated with aninstrument external to the patient for remotely energizing an in vivosensor. Interaction between the signal produced by the instrument andthe sensor is measured. The interaction is correlated with intraocularpressure.

Still other objects and advantages of the present invention will becomereadily apparent by those skilled in the art from the following detaileddescription, wherein it is shown and described in the preferredembodiments of the invention, simply by way of illustration of the bestmode contemplated of carrying out the invention. As will be realized,the invention is capable of different embodiments and its severaldetails are capable of modifications in various obvious respects,without departing from the invention. Accordingly, the drawings anddescription are to be regarded as illustrative in nature and not asrestrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

Objects and advantages of the present invention will be more clearlyunderstood when considered in conjunction with the accompanyingdrawings, in which:

FIG. 1 represents a schematic view of an embodiment of a deviceaccording to the present invention;

FIGS. 2a and 2 b represent graphs that illustrate relationships betweeninteracting exciter and responder coil-currents and frequency;

FIG. 3 represents a graph that illustrates a relationship betweennormalized signal strength and angular displacement;

FIG. 4 represents a graph that illustrates a relationship between IOPsensor pressure versus resonant frequency for S_(p)=˜5E-4pF/mmHg;

FIG. 5 represents a graph that illustrates a relationship betweenmeasured pressure and frequency;

FIG. 6a represents a top view of an embodiment of an inductor coil thatmay be included in an inductive component according to the presentinvention;

FIG. 6b is a view of an embodiment of a micro electromechanical systems(MEMS) coil that may be included in a device according to the presentinvention;

FIG. 7 represents a graph that illustrates relationships between the logof the magnitude of s₁₁ and breadboard frequency and frequency in a coilaccording to the present invention;

FIG. 8 represents a cross-sectional view of an embodiment of a pressuresensitive capacitor according to the present invention;

FIGS. 9a and 9 b represent, respectively, overhead and side views of aMolteno shunt in which an embodiment of a sensor according to thepresent invention is embedded;

FIG. 10a represents a cross-sectional view of an embodiment of a deviceaccording to the present invention;

FIG. 10b represents a cross-sectional view of another embodiment of adevice according to the present invention;

FIG. 10c represents a perspective view of a portion of a patient'seyeball with the embodiment of a device according to the presentinvention implanted under the conjunctiva;

FIG. 10d represents a perspective view in which a capacitive sensorcomponent is in a retracted position in the Molteno shunt tube;

FIG. 10e represents a perspective view of a completed Molteno processdevice showing an embedded IOP sensor with the capacitive sensorcomponent placed at the distal end of the shunt tube;

FIG. 11 represents an alternate embodiment of the IOP sensor;

FIG. 12 is a block diagram that illustrates operation of a deviceaccording to the present invention;

FIG. 13 represents a perspective view of an embodiment of a pair ofspectacles including an embodiment of an instrument attached to thespectacles;

FIG. 14 represents a functional block diagram that illustrates anembodiment of a signal-processing scheme according to the presentinvention;

FIG. 15 represents a diagram that illustrates an embodiment of anexciter circuit according to the present invention;

FIG. 16 represents a diagram that illustrates a narrow band detection ofan exciter current/voltage; and

FIG. 17 represents a series of graphs that illustrate relationshipsbetween voltage and time showing a signal processing approach forintraocular pressure measurement.

DESCRIPTION OF THE PREFERRED EMBODIMENT(S)

The present invention greatly enhances a physician's ability to treat apatient suffering from end-stage glaucoma or other ill effects ofelevated intraocular pressure by providing the physician with thecapacity to continuously monitor IOP. A significant advantage of thepresent invention is that the patient need not visit the physician tohave their intraocular pressure monitored. In fact, informationconcerning a patient's intraocular pressure may be delivered to aphysician over data communications networks such as a telephone and aninternet appliance.

A significant benefit of the present invention is that it overcomesproblems and doubts concerning indirect determination of intraocularpressure. Indirect measurements are suspect at least in part because ofconcerns related to correlation, accuracy, and consistency in relatingmeasurements to actual aqueous humor hydrostatic pressure.

By permitting continuous outpatient monitoring of intraocular pressure,the present invention permits physicians to promptly and accuratelydetect ocular hypertension, and it will enable them to select the mostefficacious treatment for the patient. The present invention will alsomake it possible to detect occult spikes in intraocular pressure and canmake a patient aware of these events so that medical attention will besought more promptly. In summary, the present invention provides anambulatory intraocular pressure monitoring system that represents arevolutionary approach in glaucoma research and clinical management.

The system according to the present invention includes an in vivo sensorand an instrument external to the patient for remotely energizing thesensor. The sensor includes a capacitive pressure sensor and aninductive component. The instrument remotely measures the pressure inthe eye, provides readout of pressure values and energizes the sensor,thereby permitting the instrument to determine the patient's intraocularpressure. Typically, at least a portion of the sensor directly contactsthe aqueous humor of the patient, thereby making the determinations ofintraocular pressure direct measurements. Since the sensor is in vivo,it is available to take measurements anywhere at any time.

To facilitate its operation, the sensor according to the presentinvention typically does not require a power source. Such a “passive”sensor will not require maintenance with respect to replacing a powersource. Also, a passive sensor does not have associated issues withrespect to adverse impact of implanting a power source in or near apatient's eye. Along these lines, the present invention minimizes thechance of infection or epithelial downgrowth at the implant site. Otheradverse effects could result from degradation of a power source underphysiological conditions and adverse affects on the patient's eye as aresult thereof.

As a passive sensor, the present invention may include an inductor inwhich a current is induced by the patient external instrument. Theinductor may be connected to an element that provides a pressuremeasurement. One example of such an element is a pressure sensitivecapacitor in which the capacitance varies with pressure exerted on thecapacitor.

The sensor is energized by the instrument's exciter coil. To accomplishthis, the instrument may include a power source and an exciter (coil)connected to the power source for supplying electric current to theexciter. Supplying power to the exciter results in energizing thesensor.

In a device according to the present invention that includes a sensorand instrument such as those described above, the sensor and instrumentmay be considered magnetically coupled. Along these lines, the inductormay include a coil, which may be referred to herein as a responder coil.The exciter may include an exciter coil. In such an arrangement, thesensor can be powered by a “link field” produced by the exciter that haselectrical properties affected by the state of the sensor. Thus, theexciter condition is related to the pressure acting on the sensor.

FIG. 1 illustrates the magnetic coupling of the responder coil 1 and theexciter coil 3. According to physical principles, the current flowing inthe exciter coil generates a magnetic field that interacts with theresponder coil. The responder coil may have a fixed inductance thatresonates with a separate pressure dependent capacitance. Thisconfiguration differs from certain known configurations in which aself-capacitance of a coil pair is resonated with the coil inductanceand both the inductance and capacitance are varied with pressure. In thearrangement shown in FIG. 1, the exciter coil is “near-field”magnetically coupled to the responder coil of the sensor. This inductivelink is noise tolerant and suited for in vivo sensorreception-transmission of energy/data.

The exciter coil and the responder coil are both resonant circuits. Theexciter coil can be made to resonate over the resonant frequency rangeof the sensor. Changes in intraocular pressure alter the capacitance ofthe pressure sensitive capacitor 5, thereby altering the resonantfrequency variation of the responder coil. A power source 7 and aprocessor 9 may be included in a circuit with the exciter.

FIGS. 2a and 2 b represent graphs that provide an electrical analysis ofthe magnetically coupled circuit shown in FIG. 1. The values shown inFIGS. 2a and 2 b were produced utilizing a responder coil that included2 turns having a diameter of about 12 mm. The exciter coil in thissystem included three turns having a diameter of about 60 mm. The twocoils were separated by about 20 mm. The exciter coil is made tobroadband resonate over the narrow-band resonant frequency range of thesensor. In the system that produced the results shown in FIGS. 2a and 2b, pressure was a parameter. The capacitor pressure sensitivity wasassumed to be dC(P)/dP=S_(p)=˜5E-4pF/mmHg.

With an intraocular pressure sensor including two circuit elements, theresponder coil and a pressure variable capacitor transducer, as theacting pressure increases there is a corresponding increase incapacitance. The coil and transducer are connected together forming whatis commonly referred to as an LC-circuit. The stimulator and powersource can provide repetitive frequency sweeps of electromagnetic energyto the sensor. The stimulator frequency would be swept over asufficiently wide range to ensure that the implanted LC circuit would beinduced to “ring” at its resonant frequency.

A current is induced in the sensor circuit by magnetic waves supplied bythe stimulator circuit. The resonant frequency is inversely related tothe intraocular pressure. In other words, the instrument includes anexciter inductive coil to magnetically near-field couple to the sensorthrough mutual inductance.

The resonant frequency may be determined from the Equation 1 below.

F _(r)(p)=(2πL×C(p))^(−½)  (1)

According to Equation 1, a pressure increase (decrease) causes theintraocular pressure sensor's resonant frequency to decrease (increase).Measuring the sensor's resonant frequency makes it possible to determinethe pressure acting on the sensor.

Near the responder resonance, however, there is a significantlyincreased coupling to the exciter. In this case an absorption dipoccurs. The nature of this dip depends on a number of factors, which caninclude the relative orientation of the two coils, the distance betweenthe coils' centers, and their electrical quality factor (Q).

The amount of coupling between the coils is also a function of the areathrough which the magnetic field passes. Maximum coupling occurs for thegreatest cross-sectional area. This is an important factor that relatesto the relative orientation of an IOPS and measurement unit. As theangle between coils, which is measured as the angle between the coilarea vectors with the coils rotating on parallel axes, changes from 0 to90 degrees, the depth of the dip follows a curve that lies between acosine and cosine squared behavior, as illustrated in FIG. 3. Thetheoretical relationship between coil orientation and “signal strength”can be derived from these measurements.

FIG. 4 represents a graph that illustrates a predicted relationshipbetween pressure and resonant frequency derived for the coilconfiguration utilized to produce the results shown in FIGS. 2a and 2 b.Therefore, FIG. 4 indicates the sensor resonant-frequency shift thatwould be expected as a function of intraocular pressure. This frequencyvariation is measured, and may be related to the sensor intraocularpressure, as described in greater detail below.

FIG. 5 represents an experimentally determined graph that illustratesthe relationship between pressure and resonant frequency utilizing dataexperimentally obtained from a laboratory apparatus. FIG. 5 alsoillustrates a curve fit to the experimental data. In comparing FIGS. 4and 5, it can be seen that FIG. 5 confirms the operation and accuracy ofthe device according to the present invention.

As described above, the magnetically coupled sensor and instrument mayeach include a coil. The composition of the material making up thesensor and instrument coils as well as the design of each of the coilsmay vary. With respect to the design, the number of turns making up thecoils, the diameter of the coils, the thickness of the material makingup the coils, the separation of each turn, and other parameters mayvary. Additionally, the orientation of the coils with respect to eachother may also vary.

FIGS. 6a and 6 b illustrate an embodiment of a sensor coil according tothe present invention. The sensor coil 11 shown in FIGS. 6a and 6 bincludes five turns with leads 12 extending in opposite directionstherefrom. FIG. 6 shows the coil and a Molteno implant 13 that the coilis arranged within. Although the coil is shown in association with aMolteno implant, any known, approved and accepted glaucomapressure-reducing fluid shunts (GPRFS), such as Molteno, Krupin, orAhmed devices, as well as any associated surgical practice may beutilized. According to another embodiment, the coil includes 9 turns.

Each end of the coil terminates in a lead having a length of about 3 mm.The coil has an outer diameter of about 4.55 mm and an inner diameter ofabout 3.75 mm. The width of the material making up to coil is about 0.05mm. Each turn of the coil is separated from adjacent turns by about 0.05mm. The sensor coil may or may not be planar.

Of course, the dimensions of the coil may vary. This coil's size can bescaled up or down in diameter up to a factor of 5×. Along these lines,the number of turns in the sensor coil may be from 1 to more than 50.

The materials making up the sensor and instrument coils may vary.Examples of materials include 36 AWG (125 μm D) copper wire, copperfoil, copper- beryllium foil, copper-plated beryllium-copper, aluminum,gold, and other materials.

With some applications, certain materials may provide betterperformance. This is demonstrated by the results represented in thegraph shown in FIG. 7, which illustrates relationships between the logof the magnitude of s₁₁ and breadboard frequency and frequency in a coilaccording to the present invention. S₁₁ is known as the input microwavescattering parameter of the IOP resonant sensor circuit. It is roughly ameasure of the power that is absorbed by the circuit when fed by agenerator.

The graph shown in FIG. 7 illustrates results obtained with tworesponder coils, one flat-wound coil made with five-turns of 36 AWG (125μm D) copper wire and the other a flat coil, micro electromechanicalsystems (MEMS) fabricated copper-plated beryllium-copper inductor (five75 μm T×125 μm W turns). The coupling angle and spacing are the same forboth coils. The deeper dip of the Cu plated beryllium-copper coil is dueto a higher Q inductor.

With respect to the present invention, in the graph shown in FIG. 7, the“dips” that appear at particular frequencies indicate the resonantfrequencies and qualities of the two forms of coil, breadboard orhand-wound wire and MEMS fabricated coil. The sharper and deeper the dipthe better the quality. This demonstrates that the MEMS coil is superiorto the breadboard coil.

Microsystem Technology or MEMS Technology is the integration ofminiaturized components of sensor applications using newly developedminiaturization techniques. Microsystems combine microelectroniccomponents (Integrated Circuits) with micromechanical or micro-opticalcomponents. The microelectronic element employs standard semiconductortechnology to analyze and manage the output data of the micromechanicalor optical element. Microsystem Technology is strategically important tomany industries and applications. Microsystems offer the possibility tominiaturize and integrate sensors, provide more intelligent sensingelectronics and electronic controls, and enhance key elements found inmany applications.

Microsystem technologies can be found in manufacturing, automotive,aircraft, security, environmental, construction, medical, andcommunication applications. Important branches of industry that willprofit from further development in microsystem technology includeelectronics, chemical, precision manufacturing, optical, and foodprocessing industries. Just as microelectronic components are found inalmost every electronic device, microsystems using micromechanicalcomponents will be as pervasive and essential in the future.

The manufacturing of the electronic portion of microsystems is wellunderstood and can be done in the same manner as traditionalsemiconductor production. However, the 3D-micromechanical elements aresufficiently different from mainstream semiconductor devices to requirenew process steps, such as wafer bonding, and manufacturing equipment,although still capable of mass quantity production.

MEMS technology is applicable to a variety of fields. One of the firstmicrosystem applications, the pressure sensor, uses the combination ofmechanical sensing elements and electronic circuitry. Themicromechanical components are produced on silicon wafers, a materialwell known in chip manufacturing. Consequently, it is possible toprocess both mechanical and electronic elements on the same siliconsubstrate. In addition to the extraordinary mechanical and electricalproperties, silicon also provides exceptional chemical properties. Thethree dimensional silicon microsystems with its multifaceted electrical,mechanical, and chemical properties have a variety of applicationpossibilities, including miniaturized pressure and acceleration sensorsused in the automobile for airbags, in-situ tire pressure gauges,emission measurements, and engine control. Additionally, MEMS technologycould be utilized ink jet heads with capillaries and micro valves thatmeter the application of ink on paper in increments of one thousandth ofa millimeter. Also, MEMS technology makes it possible to produce pumpsand motors the size of a fly's head for metering chemicals. DNA analysisthat performs millions of simultaneous process steps could be carriedout utilizing MEMS technology. Furthermore, MEMS technology could beused in micro lenses and micro switches with diameters smaller than ahuman hair used in fiber optic circuits for communication and lightningfast Pcs.

Similar to the design of the coils, the fabrication of the coils may beaccomplished in a variety of ways. The following discussion applies toboth the exciter and responder coils. In the event that the coil is aMEMS coil, the coil may be fabricated as follows. A layer of anelectrically conducting material is provided on a substrate. The layerof electrically conducting material is coated with photoresist. Next,the photoresist is exposed and developed to expose portions of the layerof electrically conducting material. Then, the exposed portions of thelayer of electrically conducting material are etched. The photoresist isstripped. Subsequently, the substrate and remaining portions of thelayer of electrically conducting material are separated.

According to a particular embodiment, two and three mil beryllium copperfoil may be waxed down to an aluminum substrate. The beryllium copperfoil may then be coated with negative acting, dry-film photoresist. Thephotoresist-coated beryllium copper foil was then patterned using aprocessed photoplot of the artwork. After exposure and development, theberyllium copper foil was spray etched using a ferric chloride solution.After etching, the remaining photoresist was stripped from the coils.The substrate with the etched coils was placed in acetone, whichdissolved the wax holding the coils to the aluminum substrate. Anothercoil configuration would have microelectronic circuit processing appliedto make miniature coils on a substrate surface. A coil also can befabricated using precision winding techniques for making wire-woundcoils.

As with the design and fabrication of the coils, the capacitor may havedifferent designs and methods for making them. FIG. 8 illustrates across-section of one embodiment of a capacitor according to the presentinvention. The embodiment illustrated in FIG. 8 is a MEMS silicondiaphragm capacitor pressure sensor. A similar device is described byKevin, H. et al., A VERSATILE POLYSILICON DIAPHRAGM PRESSURE SENSORCHIP, IDEM 91, pp. 761-764, 1991, the entire contents of which arehereby incorporated by reference. The capacitor includes a chip carrier15 on which a region of silicon 17 and contacts 19 and 21 sit. A layerof electrically conducting material 23 is arranged on silicon layer 17.Lead 25 connects electrically conducting layer 23 to contact 21. Regionsof dielectric material 27 are arranged on portions of electricallyconducting region 23. A region of silicon 29 contacts the dielectricregions 21, leaving an air gap 31 between the silicon region 29 and theelectrically conducting region 23. A layer of electrically conductingmaterial 33 is arranged on the silicon region 29. Any electricallyconducting material may be utilized. In the embodiment shown in FIG. 8,the electrically conducting material 33 is gold. A lead 35 connectscontact 19 with electrically conducting layer 33.

The capacitor shown in FIG. 8 would be attached to the leads of theresponder coil shown in FIGS. 6a and 6 b.

A variety of methods may be utilized to make the pressure sensitivecapacitor depending at least in part upon the design of the capacitor.These include using available integrated circuit or MEMS fabricatingtechnology.

The sensor, including the responder coil and the pressure sensitivecapacitor may be enclosed and/or encapsulated suitable for implantationinto a patient. The enclosure and encapsulation materials arebiocompatible. To facilitate the functioning of the present invention,the enclosure provides a connection between the pressure sensitivecapacitor and the patient's aqueous humor. This direct connection inpart is responsible for the tremendous benefits achieved according tothe present invention.

The enclosure or “packaging” of the sensor may vary, depending upon theparticular application. Two examples of packaging configuration areshown in FIGS. 10a and 10 b. A first example (FIG. 10a) of a sensor isself-contained and applicable to ambulatory animal/human subjects. Itrecords a continuous record of intraocular pressure unmodified bypressure reducing loss of anterior chamber fluid. Such data can be veryimportant for medical research pertaining to the etiology of oculardiseases and conditions caused by or causing abnormal intraocularpressure (IOP), such as glaucoma diseases and conditions. Such data hasbeen unavailable in the past, advancing both treatment and medicalknowledge.

A second example of sensor (FIG. 10b) may be utilized withkeratoprostheses. This device can be configured to enable anophthalmologist to measure IOP with a remote sensing hand heldinterrogator. Because glaucoma is a frequent complication, this sensormay be incorporated into a glaucoma pressure-reducing fluid shuntimplanted with a keratoprosthesis. Any known, approved and acceptedglaucoma pressure-reducing fluid shunts (GPRFS), such as Molteno,Krupin, or Ahmed devices, as well as any associated surgical practicemay be utilized. In general, a sensor of the second type described abovecould be incorporated in one or more types of GPRFS used in thetreatment of advanced stages of glaucoma. The present invention permitsboth physician and patient to conveniently and remotely monitor IOPduring treatment, from hospital, home, or any other location.

The examples of sensor “packaging” described above typically onlyinvolve changes in the housing that encloses the sensor. Actually, bothsettings are ambulatory, may utilize the same sensor and instrument todetermine intraocular pressure. Additionally, both examples of“packaging” include biocompatible housings as described in greaterdetail herein.

The first example of a sensor can incorporate micro electromechanicalsystems (MEMS) components that can include a miniature inductor andpressure sensitive capacitor. An external data acquisition module, suchas the instrument described herein, may be included with the first typeof sensor for remotely interrogating the intraocular pressure sensor andrecording pressure measurements for immediate or subsequent read out bya local or remote computer using application specific software, viawireless link, a modem, or via the internet, for example. Accordingly,the device may include a memory for storing the measurements.

The first example of a sensor directly and continuously measuresunmodified intraocular pressure of the aqueous humor; the second exampleof a sensor obtains measurements of modified pressure during thetreatment of elevated intraocular pressure. This second type of sensorwould be measuring modified pressure.

In some cases, devices according to the present invention will provideaccurate IOP data that may not be obtainable in other ways. For example,a device according to the present invention may be utilized whenkeratoprostheses do not respond to various tonometer methods.

FIGS. 9a and 9 b represent overhead and side views of a Molteno shunt inwhich a sensor according to the present invention is embedded. Thesensor 69 includes a responder coil 71 and a pressure sensor 73incorporated therein.

FIGS. 10a and 10 b illustrate in greater detail devices according to thepresent invention incorporated into two different types of implants.Along these lines, FIGS. 10a and 10 b, respectively, illustrate anexample of each of the two above-described types of implementations of asensor according to the present invention. In FIG. 10a, the sensor,including the coil 81 and capacitor 83, is incorporated into an implant85 made of biocompatible material. A shunt or stent 87 extends from thebody of the implant. Typically, the shunt leads to the anterior chamberof the patient's eye. The diameter of the shunt can vary. According toone embodiment, the shunt tube has a 20-30 mil inside diameter. Theshunt provides a connection to deliver the aqueous humor into theinterior of the implant where the sensor is located. As described above,the implant of this first example of a sensor does not provide means forrelieving pressure. Therefore, the implant shown in FIG. 10a shouldprovide an accurate measurement of unmodified patient IOP.

Typically, the implant is just large enough to accommodate the respondercoil. The implant shown in FIG. 10a has an outer diameter of about 0.5inch. At its widest, the pressure sensitive capacitor has a diameter ofabout 0.15 inch.

Unlike the implant shown in FIG. 10a, the implant 89 shown in FIG. 10bincludes a pressure release function in this case in the form of apressure release surface 91. The aqueous humor is delivered to theimplant through shunt 90. Both embodiments are implanted under theconjunctiva of the patient's eye. However, only FIG. 10b illustrates theconjunctiva 93. The pressure sensor is attached to the external scleraof the patient's eye and protrudes into the anterior chamber via sclerapenetration posterior to the limbus. A miniature pressure-sensitivecapacitor is thus immersed in the aqueous humor supplied from theanterior chamber. The IOP is applied to the capacitor as indicated byarrows 95. Arrows 97 indicate the pressure release by diffusive transferto the surrounding body space.

FIG. 10c provides a perspective view of the embodiment shown in FIG. 10bimplanted in a patient. Similarly, FIG. 10e illustrates a sensor 111according to the present invention arranged in a Molteno implant disk.109

In FIG. 10d the capacitive MEMS sensor 111 component is in a retractedposition so as not to interfere with the surgical placement and trimmingof the shunt tube. This tube once positioned is then cut to length asrequired. Following this trimming procedure a “thread” 115 attached tothe sensor is pulled, using a suitable surgical instrument, therebybringing the MEMS sensor to 111 a location near the end of the tube. Anyexcess thread length is cut and removed.

FIG. 11 illustrates a stand-alone device 117 that has been encapsulatedwith a biocompatible material. In the embodiment shown in FIG. 11, allof the device, including the responder inductor coil 119, has beenencapsulated except for the capacitor 121 so that the aqueous humor canact directly on the capacitor.

Other forms of the sensor can include a membrane type that can be placedon various locations of the eye globe including about the cornea. Ofcourse, these represent just a few examples of possible implementationsof the present invention. Additionally, with the advent of the newermicro-robot technology, implantable aqueous “pumps” could be developedwhich could be incorporated into a feedback system that automaticallyregulates intraocular pressure.

Unlike the sensor according to the present invention, the instrument isexternal to the patient. No wired connection is made between the sensorand the instrument. This is what is meant by remote when referring tothe energizing of the sensor, for example. FIG. 12 shows elements thatmay be included in an instrument. These elements include, among others,an exciter coil 123, a sweep generator 125, an RF generator 127, anenvelop detector 129, a resonance detector 131, a digitizer 135, adisplay or readout 137, and data storage 139. The responder coil 141 hasbeen implanted in the eye 143.

As described above, the instrument exciter coil may be magneticallycoupled to the sensor. The exciter coil may include any number of turnsnecessary to permit the exciter to function in energizing the sensor andthen determine the intraocular pressure based upon interaction with thesensor. The coil is connected to a power source, as is illustrated inFIG. 1.

The instrument can be worn by the patient, for example, attached to orincorporated in spectacles worn by a patient. FIG. 13 shows anembodiment that includes an instrument 145 attached to a pair ofspectacles 147. The instrument could also be incorporated into thetemple of the spectacles. Any other arrangement could be utilized aslong as it permits the instrument to be located a distance from and inan orientation with respect to the sensor 149 that permits the device tofunction properly. Typically, the instrument is arranged about 1 cm toabout 2.5 cm away from the sensor.

In addition to the exciter coil and power supply, the instrument couldinclude a memory device for displaying and/or recording results ofenergizing of the sensor. The memory could include any commonlyavailable memory, such as any solid-state memory device, for example anyrandom access memory (RAM), which could potentially store millions ofmeasurements, using currently available memory technology. The resultsof the energizing of the sensor could be converted to correspondingvalues for intraocular pressure, which could then be stored in thememory.

Furthermore, the instrument may include a processor for carrying out oneor more tasks. The tasks that a processor could carry out can includecontrolling the energizing of the instrument. This may includecontrolling delivery of power to the exciter coil. Details of thecarrying out of the excitation are described below. The processor mayalso or alternatively translate the results of energizing of the sensorinto values of intraocular pressure. Additionally, the processor orother circuitry could convert measurements of IOP into a digital format,which may be stored in the memory.

In addition to or in place of a processor located in the instrument, thedevice could include a processor remote from the instrument. In suchembodiments, one or more of the functions performed by the processor inthe instrument could be performed by the remote processor.

In addition to the above, utilizing miniaturized circuitry, a datalogger including the memory, processor and/or other circuitry could bebuilt into the spectacle's frame. The data logger could also have theability to download the stored data into an office-based computer forfurther processing.

To permit a patient and/or physician to act in cases where intraocularpressure deviates from a certain value or range of values, theinstrument may include an indicator. Typically, the indicator indicateswhen pressure exceeds a stored threshold value. Any type of indicatormay be utilized. Along these lines, the indicator may be visual,audible, tactile, and/or otherwise. For example, the indicator mayinclude one or more lights incorporated into the instrument.Alternatively, the indicator may generate sound to signify theintraocular pressure differs from a predetermined value or range ofvalues. Also, the indicator may vibrate. Some embodiments of theindicator may include a wireless connection that signals a caregiverthat the pressure differs from the predetermined value or range ofvalues.

To function as described above, the instrument typically includescircuitry for detecting and processing signals related to theinteraction between the exciter coil and the sensor coil and pressuresensitive capacitor. With respect to signal processing and circuitdesign for the measurement of pressure via the resonant dip affectdescribed above, FIG. 14 provides a block diagram of a system thatoutputs a voltage proportional to the pressure “seen” by the system.

FIG. 15 illustrates an example of an exciter system. In the system shownin FIG. 15, a low frequency, such as on the order of about 250 Hz,oscillator (LFO) generates a triangle wave output. This triangle wavemodulates a radio frequency voltage controlled oscillator (VCO). In thesystem shown in FIG. 15, the VCO nominal output frequency, on the orderof about 100 Mhz, is swept back and forth between the VCO minimum andmaximum frequencies at the 250 Hz rate of the LFO. The VCO amplitude isfairly constant over the narrow sweep range of about 1 MHz.

The exciter circuit is tuned to broadband resonate at the same frequencyas the responder circuit. As described above, at this point a dip occursin the current amplitude of the exciter coil at the resonant frequencyof the responder circuit. Since the frequency of the dip minimum is ofprimary interest, the VCO sweep range is typically set to cover a rangein the vicinity of the dip minimum for the maximum frequency variationexpected for the pressure range being measured. As a function of time,the frequency sweep may be repeated at the frequency of the LFO. Anenvelope detector may produce a dc-voltage proportional to thepeak-to-peak amplitude of the RF signal across the exciter coil. Thus,in this case, the output of the envelope detector will look like thesignals shown in FIG. 16.

The lowest point of the dip, the minimum, corresponds to the resonantfrequency of the responder circuit. The dip will be in the middle of thesweep interval at ambient pressure and will move to the left, towardf_(min), as the pressure increases. Thus, the location of the dip in thesweep interval will be an indication of the pressure seen by theresponder circuit.

Trying to measure the frequency where the dip occurs during the sweepinterval can be difficult so an alternate approach may also be utilized.This approach is based on the duty cycle of the sweep interval. The dutycycle is the ratio of the time from the dip to the end of the sweepinterval to the total time of the sweep interval. Thus, at ambientpressure, the dip is in the middle of the sweep interval and the dutycycle is therefore 50%. As the pressure increases and the dip movestoward f_(min), the duty cycle may increase. Thus, the signal processingpath shown in FIG. 13 converts the envelope detector's output into asignal whose duty cycle is proportional to pressure.

FIG. 17 illustrates signal waveforms at various points in the signalprocessing path for both ambient pressure, i.e. graphs 1, 3, 5 and 7,and at a pressure greater than ambient, i.e. graphs 2, 4, 6 and 8.Graphs 1 and 2 illustrate the output of the envelop detector, graphs 3and 4 illustrate the output of the differentiator, graphs 5 and 6illustrate the output of the zero crossing detector and graphs 7 and 8illustrate the output of the synchronous divide by 2. In all of thegraphs, the vertical axis is voltage and the horizontal axis is time.The output of the differentiator, shown in graphs 3 and 4, is a measureof the slope of the output of the envelope detector signal, shown graphs1 and 2. When the slope of the envelope detector signal is negative theoutput of the differentiator a will be a negative voltage, i.e. belowground or zero volts. When the slope of the envelope detector signal ispositive the output of the differentiator will be a positive voltage,i.e. above ground or zero volts. When the slope is zero, i.e. at thebottom of the dip, the output of the differentiator is zero volts. Thezero crossing detector output, i.e. graphs 5 and 6, simply indicates ifthe differentiator output is above or below zero volts. In theory, everytime the differentiator signal crosses zero volts, the output of thezero crossing detector changes value. When the differentiator outputsignal is below zero volts the output of the zero crossing detector iszero volts and when the output of the differentiator is above ground thezero crossing detector output is +V, typically +5 volts.

At ambient pressure the output of the zero crossing detector is asymmetrical waveform with 50% duty cycle, i.e. graph 5. However, atpressures greater than ambient, the zero crossing detector outputsignal, illustrated in graph 6, is not symmetrical and its duty cyclehas not actually changed significantly. Dividing the zero crossingdetector output signal by 2, i.e. graphs 7 and 8, results in a signalwhose duty cycle is again 50% at ambient pressure, i.e. graph 7, andsignificantly greater than 50%, i.e. graph 8, at a pressure greater thanambient. A simple integrator then converts the output of the dividerinto a voltage. This final voltage is now directly proportional to thepressure seen by the responder circuit. This approach simplifies thedata acquisition to one of measuring a dc voltage instead of afrequency.

Analysis and characterization of the exciter-responder link can takeinto account variations in physical, environmental, electrical andorientation properties. For example, the device according to the presentinvention can take into account barometric pressure and provide a recordof this influence. The data may be recorded and/or output as it issensed and corrected for barometric pressure. Also, ambient temperatureis also a factor that may be correct for and could be taken into accountby temperature specific calibration tables. For animal/human intraocularpressure measurement, the subject's nominal temperature may be input tothe device. The temperature compensation could be automatic and inreal-time.

Automatic temperature compensation may be accomplished with the additionof a thermocouple attached to the patients skin near the eye. The signalfrom the thermocouple would be processed to provide an offset correctionsignal, much the same way the local barometer corrects for local ambientpressure effects.

Sensor calibration may be carried out utilizing an apparatus thatapplies known hydrostatic pressure to an in vitro sensor. Each unit'scalibration table may be loaded into memory in the intraocular pressuremonitor and used to “linearize” response. Sensor calibration is wellknown to those skilled in the art.

The present invention also includes a method for measuring intraocularpressure of a patient. According to the method, a signal is generatedwith an instrument external to a patient to energize an in vivo sensorthat is affected by intraocular pressure. An interaction between thesignal produced by the instrument and the sensor is measured. Theinteraction is correlated with intraocular pressure.

First, the sensor may be implanted in a patient's eye. This may firstinvolve inserting the sensor into one of the devices described above,such as a Molteno device. Alternatively, the sensor may be encapsulatedin other biocompatible material. Implanting the sensor, whether enclosedin a known device or encapsulated in another material, may be carriedout according to standard surgical procedures.

As described above, the instrument, including the coil and power source,may provide repetitive bursts of high frequency energy to the implantedsensor. The instrument frequency would be swept over a sufficiently widerange to ensure that the implanted sensor circuit would be induced to“ring” at its resonant frequency.

The present invention permits real-time continuous intraocular pressuredata to be measured over any period of time. For example, period of timecould cover a twenty-four hour period. In the event the instrumentproduces analog output, the output could be converted for digitalrecording on a disk drive. Along these lines, the instrument could beprogrammed for data acquisition duty cycle. Initial recordings may beduty cycled to obtain both continuous fast-time-response data, such ason the order of less than about 50 msec, and lower resolution averagedata. Duty cycling may reduce the demand for storage capacity, more inkeeping with data capacity on a small, portable self-containedintraocular pressure measurement system. However, this limitation maynot be an issue with data that can be real-time routed to high capacitystorage via a wireless or wired connection.

The device may be controlled to determine intraocular pressure atregular intervals. The timing of the intervals may vary. One factor thatmay control the timing of the determination of intraocular pressure isthe rate of change of the pressure. Along these lines, if it isdetermined that the rate of change of the pressure is increasing, thenthe rate of determination may be increased. Any other regimen may beutilized in controlling the determination of intraocular pressure.

The method can include transmitting the intraocular pressure values, inthe form of raw data or after first converted to the actual pressurevalues, to a processor remote from the instrument. A processor that thevalues are transmitted or downloaded to could be part of a computer thatincludes software for determining trendline data, statistical summariesof the maximum and minimum pressures, and/or the percentage of time thatthe intraocular pressure was “controlled.” Sensor performancemeasurements could include time/frequency response, hysteresis, drift,and stability.

The foregoing description of the invention illustrates and describes thepresent invention. Additionally, the disclosure shows and describes onlythe preferred embodiments of the invention, but as aforementioned, it isto be understood that the invention is capable of use in various othercombinations, modifications, and environments and is capable of changesor modifications within the scope of the inventive concept as expressedherein, commensurate with the above teachings, and/or the skill orknowledge of the relevant art. The embodiments described hereinabove arefurther intended to explain best modes known of practicing the inventionand to enable others skilled in the art to utilize the invention insuch, or other, embodiments and with the various modifications requiredby the particular applications or uses of the invention. Accordingly,the description is not intended to limit the invention to the formdisclosed herein. Also, it is intended that the appended claims beconstrued to include alternative embodiments.

We claim:
 1. A method for measuring intraocular pressure of a patient,the method comprising: generating a signal with an instrument externalto the patient for remotely energizing an in vivo sensor; measuringinteraction between the signal produced by the instrument and thesensor; correlating the interaction with intraocular pressure; recordingthe correlated intraocular pressure; wherein the instrument generates asignal at varied intervals; and wherein the interval decreases as a rateof change of intraocular pressure increases.
 2. The method according toclaim 1, further comprising: providing an alarm for indicating whenintraocular pressure differs from a predetermined value.